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The process of protein synthesis can be divided into three main phases : initiation, during which the ribosomal subunits join the mRNA and locate the AUG initiator codon; elongation, during which sense codons are decoded and the bulk of the polypeptide is made; and termination, during which a stop codon directs the release of the completed polypeptide from the ribosome. Whereas the general principles of sense codon decoding by transfer RNAs are well established, a clear picture of translation termination and stop codon recognition has hitherto been lacking. Recently however, the use of optimized, complex, reconstituted in vitro termination reactions to identify the roles of key termination factors, and the solution of tertiary structures of termination factors, has allowed a reappraisal of termination factor structure and function. This review will describe these recent advances, many of which have resulted from studies of termination in micro-organisms, and in the light of the new information, discuss models for the mechanism of termination and recognition of the stop codon. While the mechanism of peptide chain termination is normally effective, stop codons are not always recognized efficiently, and during the translation of certain viral RNAs can be suppressed or read through, resulting in the expression of additional coding information. How stop codons are reassigned to encode ‘sense’ at a given frequency in some RNAs will be reviewed in the context of current understanding of termination and stop codon recognition mechanisms.

Endless possibilities: translation termination and stop codon recognition